High Betaine and Dynamic Increase of Betaine Levels Are Both Associated With Poor Prognosis of Patients With Pulmonary Hypertension.

Background and Objective: The association between plasma betaine levels and cardiovascular diseases (CVDs) has been revealed except for pulmonary hypertension (PH). In this study, we aimed to explore the role of betaine in patients with PH. Methods: Inpatients with PH at Fuwai Hospital were enrolled after excluding relative comorbidities. Each patient received at least one follow-up through a clinical visit, and the fasting blood was obtained both at the first and second hospitalization for betaine detection. The primary endpoint was defined as composite outcome events and the mean duration was 14.3 (6.9, 21.3) months. The associations of betaine and changes of betaine (Δbetaine) with disease severity and prognosis were explored. Results: Finally, a total of 216 patients with PH were included and the medians for betaine plasma levels in the total patients group, low betaine, and high betaine groups were 49.8 (39.0, 68.3) μM, 39.0 (33.5, 44.7) μM, and 68.1 (57.8, 88.7) μM, respectively. High betaine was associated with poor World Health Organization Functional Class (WHO-FC), increased N-terminal pro-brain natriuretic peptide (NT-proBNP), low tricuspid annular plane systolic excursion (TAPSE), and cardiac output index even after adjusting for confounders. Patients with high betaine were over twice the risk to receive the poor prognosis than those with a low level [hazard ratio (HR) = 2.080, (95% CI: 1.033-4.188)]. Moreover, the decrease of betaine level after further treatment was positively correlated to ΔNT-proBNP indicating Δbetaine might be an effector of disease severity, and dynamic increase of betaine was also associated with poor prognosis in PH. Conclusion: Betaine was associated with disease severity and might be an effector in PH. Patients with increased levels or with dynamic rise of betaine heralded a poor prognosis.